tbuckley/cabot-search huggingface dataset:
Abstract 5926: Hepatocellular carcinoma in the hepatitis B vaccinated and nonvaccinated age groups in The Gambia
Authors: Sheikh Omar Bittaye, Ramou Njie
Journal: Cancer Research (2022)

Abstract INTRODUCTION: Hepatitis B vaccination was started in The Gambia in July 1986 and nationwide coverage was achieved in February1990. However not much is known about its effect in the prevention of Hepatocellular carcinoma (HCC) in The Gambia. OBJECTIVE: We assess the differences in the features of HCC in both the Hepatitis B vaccinated and non-vaccinated age groups in The Gambia. METHOD: Patients with suspected HCC who were referred to the main liver clinic at the Medical Research Council, Gambia Unit (MRCG) were recruited from June 2011 to September 2019. The diagnostic criteria for HCC comprised of ultrasound demonstration of liver mass ≥2 cm with or without clinical features combined with alpha-fetoprotein (AFP) level of ≥200 ng/ml and/or histopathological confirmation. Clinical, radiological, fibroelastrography and laboratory data were collected in all patients. RESULTS: Five hundred and forty two patients were recruited into the study. The majority (91.3%) of the patients were in the non-vaccinated age group and most (88.8%) were born in The Gambia. Those born outside The Gambia were mostly Senegalese, Sierreleonean, and Guineans. The patients in the vaccinated age group were much younger and less likely to be born in The Gambia. They were also more likely to have higher AFP levels, positive HBsAg and a lower creatinine level as compared to those patients in the non-vaccinated age group. There was no difference in clinical manifestations, Liver Function tests and median survival. CONCLUSIONS: The early introduction of Nationwide Hepatitis B vaccination in 1990 into the EPI program in The Gambia may have had a positive effect in the incidence of Hepatocellular Carcinoma in the vaccinated age group. Compared to neighbouring countries, The Gambia seems to be leading the path for Hepatitis B elimination.To strengthen these gains, a nationwide screening and treatment program needs to be implemented for those in the non-vaccinated age groups. Citation Format: Sheikh Omar Bittaye, Ramou Njie. Hepatocellular carcinoma in the hepatitis B vaccinated and nonvaccinated age groups in The Gambia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5926.
Twists in the fibrodysplasia ossificans progressiva story challenge and expand our understanding of BMP biology
Authors: Michael T. Collins
Journal: Journal of Clinical Investigation (2022)

Fibrodysplasia ossificans progressiva (FOP) is an ultrarare, debilitating disease in which heterotopic bone is formed in certain soft tissues. A gain-of-function variant in the cytoplasmic domain of the activin A receptor type I (ACVR1) exists in all patients with FOP. Strikingly, these FOP-causing variants imbue a neofunction to ACVR1 - the ability to recognize activin A as an agonist with bone morphogenic protein-like signaling that leads to heterotopic ossification (HO). These findings are supported by the efficacy of anti-activin A antibodies in preventing HO in FOP mice. This surprising story continues in companion papers in this issue of the JCI. Aykul et al. and Lees-Shepard et al. independently found that antibodies against ACVR1, which were being developed as potential therapeutics for FOP, instead caused HO in FOP mice. While this unexpected finding may be the clinical final act for such antibodies, it provides another twist in the unique and evolving FOP story.
Abstract 6171: A single-cell solution for solid tumors to detect mutations and quantify copy number variations
Authors: Saurabh Parikh, Khushali Patel, Alex Li, Anup Parikh
Journal: Cancer Research (2022)

Abstract Cancer is a highly heterogeneous disease characterized by the presence of chromosomal structural copy number variation (CNV) and driver gene mutation events, which appear somatically at the early stages of oncogenesis and can drive tumor progression. Previously, we have developed a high throughput single cell DNA analysis platform that leverages droplet microfluidics and a multiplex-PCR based targeted DNA sequencing approach. It demonstrates high sensitivity detection of SNVs and indels in the same cells and generation of high resolution maps of clonal architecture based on mutational profiling. Here we expand upon the same approach and create an algorithm to accurately quantify CNVs along with genetic mutations from the same single cells. To estimate the CNV the amplicon read counts were corrected for artefacts related to cell to cell variability due sequencing efficiencies along with amplicon to amplicon variability that occur due to amplification efficiency differences. We used a spiked in diploid cell line as a reference to normalize all the cells. The spiked cell line was identified using its mutational profile. We validated the system using cell lines with known CNVs and found that we could at least accurately estimate copy numbers ranging from 0 through 5. Some of the regions were also validated orthogonally using droplet digital PCR. Another set of validation was performed using well characterized cell lines from NIST. We enable multiple visualizations of the copy number estimates in karyotype plots and line plots projected on SNV clones. With improved biochemistry, panel design and novel data analysis algorithms we develop a complete solution to detect amplification or loss of function in oncogenes and tumor suppressors reliably. Integration of CNVs and SNVs facilitates more accurate reconstruction of tumor evolution to better understand cancer progression mechanisms as well for quality control of gene edited cells, to further advance cancer research and therapy. Citation Format: Saurabh Parikh, Khushali Patel, Alex Li, Anup Parikh. A single-cell solution for solid tumors to detect mutations and quantify copy number variations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6171.
Abstract 5931: Development and validation of a novel circulating cell-free microRNA diagnostic model with high accuracy for multi-cancer early detection
Authors: Andrew Zhang, Hai Hu
Journal: Cancer Research (2022)

Abstract Introduction: Early detection is critical to reduce cancer deaths as treating early stage cancers is more likely to be successful. We aimed to develop and validate a noninvasive blood-based diagnostic model capable of detecting multiple cancers by assessing the expression levels of serum microRNAs (miRNAs). Patients and Methods: Four microarray datasets assessing expression profiles of 2588 serum miRNAs with a standardized platform were assembled from Gene Expression Omnibus (GEO) totaling 7536 participants including 3604 cancer patients across 13 cancer types and 3932 non-cancer controls. A diagnostic model was built in a training set of 416 participants, including 208 lung cancer patients and 208 non-cancer controls matched for age, sex, and smoking history. The model performance was assessed in the validation sets consisting of all the remaining 7120 participants. Results: A 4-miRNA diagnostic model was developed from the lung cancer training set. The model showed 99% sensitivity and specificity in the lung cancer validation set (n=3328, 1358 cancer &amp; 1970 non-cancer participants); and the sensitivity remained to be &amp;gt;99% for patients with stage 1 disease. When applied to the additional dataset of 3792 participants including 2038 cancer patients across 12 cancer types and 1754 independent non-cancer controls, the model showed high sensitivities ranging from 83⋅2% to 100% for biliary tract, bladder, colorectal, esophageal, gastric, glioma, liver, pancreatic, and prostate cancers, and reasonable sensitivities of 68⋅2% and 72⋅0% for ovarian cancer and sarcoma, respectively, while maintaining 99⋅3% specificity (Table 1). Conclusion: The study provided a proof-of-concept demonstrating that the 4-miRNA model has the potential to be developed into a simple, inexpensive and noninvasive blood test for early detection of multiple cancers with high accuracy. Table 1. Sensitivities of the 4-miRNA diagnostic model in 12 cancer types. N Sensitivity Lung Cancer 1358 99.3% Biliary Tract Cancer 40 97.5% Bladder Cancer 392 98.2% Colorectal Cancer 155 85.8% Esophageal Cancer 124 84.7% Gastric Cancer 150 100% Glioma 40 87.5% Liver Cancer 348 84.2% Ovarian Cancer 333 68.2% Pancreatic Cancer 149 83.2% Prostate Cancer 40 92.5% Sarcoma 132 72.0% Citation Format: Andrew Zhang, Hai Hu. Development and validation of a novel circulating cell-free microRNA diagnostic model with high accuracy for multi-cancer early detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5931.
Abstract 5881: The efficacy of a technology-based support program on survivorship experience: Asian American breast cancer survivors
Authors: Eun-Ok Im, Wonshik Chee, Sudeshna Paul
Journal: Cancer Research (2022)

Abstract Purpose: A technology-based intervention without face-to-face interactions could work better for many women from cultures where breast cancer is still a stigmatizing experience. Also, a technology-based intervention could meet the necessity of information and support without time and/or geographical restrictions. The purpose of this study was to test the efficacy of a technology-based support program for Asian American breast cancer survivors (TICAA) in enhancing the women’s breast cancer survivorship experience. Methods: This was a randomized controlled intervention with repeated measures (pretest [Time Point 0; T0], post 1-month [T1], and post 3-months [T2]). A total of 199 Asian American breast cancer survivors were recruited/retained through online and offline settings and included in the data analysis. While the intervention group was requested to use the TICAA and the American Cancer Society (ACS) website on breast cancer for 3 months, the control group was requested to use the ACS website for 3 months. Multiple instruments were used: the Cancer Behavior Inventory (CBI), the Personal Resource Questionnaire (PRQ), the Perceived Isolation Scale (PIS), the Support Care Needs Survey-34 Short Form (SCNS), the Memorial Symptom Assessment Scale-Short Form (MSAS), and the Functional Assessment of Cancer Therapy Scale-Breast Cancer (FACT-B). The data were analyzed using growth curve models, fitted within the framework of mixed effects modeling, and mediation analyses. Results: Within the mixed-effect model, there were significant decreases in the needs for help scores (SCNS scores) from T0 to T2 (β = -3.0236, p = .005) and the symptom distress scores (MSAS scores) from T0 to T1 and T2 (β = -2.8131, p &amp;lt; .001; β = -3.0356, p &amp;lt; .001). Yet, the change over time in the quality-of-life scores (FACT-B scores) was not statistically significant although the fixed effect of time was significant (β = -1.0476, p = .004). All the theory-based mediators (attitudes, self-efficacy, perceived barriers, and social influences) had statistically significant mediating impact on all outcome variables (needs for help, symptom distress, and quality-of-life; all p &amp;lt; .001), but there were differences in the mediating effects among different individual outcome variables. Conclusions: The findings supported the efficacy of the technology-based program in reducing the need for help and symptoms of Asian American breast cancer survivors. Further studies are needed on the differences in the effects of theory-based mediators on different outcome variables. Citation Format: Eun-Ok Im, Wonshik Chee, Sudeshna Paul, TICAA Research Team. The efficacy of a technology-based support program on survivorship experience: Asian American breast cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5881.
Abstract 2239: Detecting cancer when it can be cured: The potential for cure across all stageable cancers
Authors: Earl Hubbell, Christina Clarke
Journal: Cancer Research (2022)

Abstract Introduction: Early detection of cancer may reduce cancer mortality by providing access to treatments with the potential to cure cancer at early stages. A mixture cure model divides cancer cases into two populations: one where cancer is likely to severely impact mortality (not-cured) and one where long-term survival with low risk is possible (cured). Previous work on such models has concentrated on estimating cure for either many cancer types without regard to stage (public health arena), or single cancers by stage at diagnosis (screening arena). A gap in the current literature is an estimation of likelihood of cure in many cancer types at all stages. Methods: We estimate a mixture-cure model for all stages simultaneously for stageable cancers using the fact that cancer is a progressive disease (worse by stage) as a constraint on model parameters. We applied this estimation procedure to 21 cancer classes with standard American Joint Committee on Cancer (AJCC) staging using 12 years of cancer-specific survival data in 50-79 year old individuals using Surveillance, Epidemiology and End Results (SEER) program data from 2006-2015 followed to 2018. For each stage, we recover the fraction of those cured (“cure fraction”, i.e., long-term survivors with minimal excess hazard) and not-cured (severe acute mortality due to cancer, modeled as a Weibull distribution). Results: Cure fractions varied between cancer classes. Two important types of cancer behavior are illustrated by colorectal and gallbladder cancers. Colorectal cancer had a good potential for cure at any stage before metastasis, with a precipitous drop from 63% (95% CI: 62-64%) cure at stage III to 7% (6-7%) cure at stage IV. In contrast, gallbladder cancer exhibited a systematic decrease at each stage, with 47% (43-52%) cure fraction at stage I, 22% (20-24%) at stage II, 20% (17-22%) at stage III, and 2% (2-3%) at stage IV. Differences in 5-year survival between earlier stages and metastasis were highly correlated to differences in cure fraction (r^2=0.97), suggesting differences in 5-year survival are a proxy for differences in cure. Conclusions: Long-term survivors were evident at early stages for all 21 cancer types examined. These survival fractions were all greatly reduced by the time cancer reached metastasis. This indicates early-stage cancers do not differ from late-stage cancers simply by lead time and provides statistical evidence that detection of cancer in early stages may result in long-term survival for many stageable cancer types. Citation Format: Earl Hubbell, Christina Clarke. Detecting cancer when it can be cured: The potential for cure across all stageable cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2239.
Abstract 467: Integrative deep learning analysis identifies cross-talk between morphology, mutation, and clinical variables for colon adenocarcinoma patient outcomes
Authors: Jie Zhou, Ali Foroughi pour, Rafic Beydoun, Hany Deirawan, Fayez Daaboul, Fahad Shabbir Ahmed, Jeffrey H. Chuang
Journal: Cancer Research (2022)

Abstract Colorectal cancer is one of the most common cancers in both men and women. Patient stratification in colorectal cancers is challenging and affects therapy decisions and patient care. In this study, we develop an integrative Inception V3-based deep learning approach to stratify TCGA-COAD patients from H&amp;E images, showing that combining deep learning extracted morphological features with clinical and mutational status improves patient stratification. Morphological features within tumor regions can distinguish patients by short or long overall survival (OS) (OS&amp;lt;3 years v.s. OS&amp;gt;5 years, AUC 0.81±0.12), while they are less informative for intermediate OS (3&amp;lt;OS&amp;lt;5 years). Models that integrate morphological features with additional data modalities yield superior stratification to those that use only a single datatype or that use only clinical information and genomic markers. Remarkably, combining deep learning morphological features with clinical information and genomic markers also boosts stratification of patients with 3&amp;lt;OS&amp;lt;5 years, both at the 3-year time point (p &amp;lt;0.001) and 5-year time point (p &amp;lt;0.001). We validated our model on an external dataset (OS&amp;lt;3 years v.s. OS&amp;gt;5 years, AUC 0.78±0.20), and again found that combining morphological features and clinical data is superior to only using a single datatype. Our deep learning models were also able to perform reliable tumor segmentation (AUC&amp;gt;0.92). However, survival predictions based on deep learning tumor segmentation were inferior to those based on pathologist tumor annotations (OS&amp;lt;3 years v.s. OS&amp;gt;5 years, AUC 0.79±0.14). Furthermore, we show that the cross-talk between different data modalities is informative of patient risk. More precisely, models that directly combine image and clinical features performed superior to a naïve Bayes classifier combining predictions of models trained on each data type (integrative model AUC=0.81±0.06 and naïve Bayes AUC=0.76±0.11, p&amp;lt;0.01). Our results show integrative analysis utilizes the cross-talk between data modalities to boost patient risk stratification, and that deep learning is an efficient methodology for taking advantage of cross-talk between various data modalities. Citation Format: Jie Zhou, Ali Foroughi pour, Rafic Beydoun, Hany Deirawan, Fayez Daaboul, Fahad Shabbir Ahmed, Jeffrey H. Chuang. Integrative deep learning analysis identifies cross-talk between morphology, mutation, and clinical variables for colon adenocarcinoma patient outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 467.
Frailty Status Modifies the Efficacy of Exercise Training Among Patients With Chronic Heart Failure and Reduced Ejection Fraction: An Analysis From the HF-ACTION Trial
Authors: Ambarish Pandey, Matthew W. Segar, Sumitabh Singh, Gordon R. Reeves, Christopher O’Connor, Ileana Piña, David Whellan, William E. Kraus, Robert J. Mentz, Dalane W. Kitzman
Journal: Circulation (2022)

Background: Supervised aerobic exercise training (ET) is recommended for stable outpatients with heart failure (HF) with reduced ejection fraction (HFrEF). Frailty, a syndrome characterized by increased vulnerability and decreased physiologic reserve, is common in patients with HFrEF and associated with a higher risk of adverse outcomes. The effect modification of baseline frailty on the efficacy of aerobic ET in HFrEF is not known. Methods: Stable outpatients with HFrEF randomized to aerobic ET versus usual care in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial were included. Baseline frailty was estimated using the Rockwood frailty index (FI), a deficit accumulation–based model of frailty assessment; participants with FI scores &gt;0.21 were identified as frail. Multivariable Cox proportional hazard models with multiplicative interaction terms (frailty × treatment arm) were constructed to evaluate whether frailty modified the treatment effect of aerobic ET on the primary composite end point (all-cause hospitalization or mortality), secondary end points (composite of cardiovascular death or cardiovascular hospitalization, and cardiovascular death or HF hospitalization), and Kansas City Cardiomyopathy Questionnaire score. Separate models were constructed for continuous (FI) and categorical (frail versus not frail) measures of frailty. Results: Among 2130 study participants (age, 59±13 years; 28% women), 1266 (59%) were characterized as frail (FI&gt;0.21). Baseline frailty burden significantly modified the treatment effect of aerobic ET ( P interaction: FI × treatment arm=0.02; frail status [frail versus nonfrail] × treatment arm=0.04) with a lower risk of primary end point in frail (hazard ratio [HR], 0.83 [95% CI, 0.72–0.95]) but not nonfrail (HR, 1.04 [95% CI, 0.87–1.25]) participants. The favorable effect of aerobic ET among frail participants was driven by a significant reduction in the risk of all-cause hospitalization (HR, 0.84 [95% CI, 0.72–0.99]). The treatment effect of aerobic ET on all-cause mortality and other secondary endpoints was not different between frail and nonfrail patients ( P interaction&gt;0.1 for each). Aerobic ET was associated with a nominally greater improvement in Kansas City Cardiomyopathy Questionnaire scores at 3 months among frail versus nonfrail participants without a significant treatment interaction by frailty status ( P interaction&gt;0.2). Conclusions: Among patients with chronic stable HFrEF, baseline frailty modified the treatment effect of aerobic ET with a greater reduction in the risk of all-cause hospitalization but not mortality.
Abstract 235: Differential polyamine expression in human pancreatic cancer supports the use of polyamine blockade therapy to modulate the <i>in vivo</i> pancreatic tumor microenvironment
Authors: Sai Preethi Nakkina, Sarah B. Gitto, Veethika Pandey, Jignesh Parikh, Dirk Geerts, Carlo Maurer, Kenneth P. Olive, Otto Phanstiel, Deborah A. Altomare
Journal: Cancer Research (2022)

Abstract Pancreatic cancer has a poor five-year survival rate of less than 8% and is projected to be the second leading cause of cancer related deaths in the US by the year 2030. Polyamine metabolism is an underexplored therapeutic target in pancreatic ductal adenocarcinoma (PDAC). The current investigation profiled RNA expression of genes associated with polyamine metabolism, transport and homeostasis in clinical pancreatic cancer samples to reveal evidence for dysregulation of polyamine-based pathways in PDAC. Increased expression of select pro-polyamine genes was associated with poorer patient prognosis in data obtained from the TCGA dataset. Preclinical experimental data supported the use of polyamine blockade therapy (PBT) in pancreatic tumor bearing mice, and revealed that PBT increased survival and decreased tumor weights in comparison to control treatment. PBT therapeutic effects were associated with increased expression of CD86 T cell co-stimulatory marker present on antigen presenting cells in the tumor microenvironment. Collectively, polyamine dysregulation in human pancreatic cancer is associated with poorer patient prognosis, whereas PBT treatment resulted in improved in vivo therapeutic outcomes in part through immune modulation in the tumor microenvironment. Citation Format: Sai Preethi Nakkina, Sarah B. Gitto, Veethika Pandey, Jignesh Parikh, Dirk Geerts, Carlo Maurer, Kenneth P. Olive, Otto Phanstiel, Deborah A. Altomare. Differential polyamine expression in human pancreatic cancer supports the use of polyamine blockade therapy to modulate the in vivo pancreatic tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 235.